9: Metals in Medicine (2023)

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    Metal ions are required for many critical functions in humans. Scarcity of some metal ions can lead to disease. Well-known examples include pernicious anemia resulting from iron deficiency, growth retardation arising from insufficient dietary zinc, and heart disease in infants owing to copper deficiency. The ability to recognize, to understand at the molecular level, and to treat diseases caused by inadequate metal-ion function constitutes an important aspect of medicinal bioinorganic chemistry.

    Metal ions can also induce toxicity in humans, classic examples being heavy-metal poisons such as mercury and lead. Even essential metal ions can be toxic when present in excess; iron is a common household poison in the United States as a result of accidental ingestion, usually by children, of the dietary supplement ferrous sulfate. Understanding the biochemistry and molecular biology of natural detoxification mechanisms, and designing and applying ion-specific chelating agents to treat metal overloads, are two components of a second major aspect of the new science that is evolving at the interface of bioinorganic chemistry and medicine.

    Less well known than the fact that metal ions are required in biology is their role as pharmaceuticals. Two major drugs based on metals that have no known natural biological function, Pt (cisplatin) and Au (auranofin), are widely used for the treatment of genitourinary and head and neck tumors and of rheumatoid arthritis, respectively. In addition, compounds of radioactive metal ions such as 99mTc and complexes of paramagnetic metals such as Gd(III) are now in widespread use as imaging agents for the diagnosis of disease. Many patients admitted overnight to a hospital in the U.S. will receive an injection of a 99mTc compound for radiodiagnostic purposes. Yet, despite the obvious success of metal complexes as diagnostic and chemotherapeutic agents, few pharmaceutical or chemical companies have serious in-house research programs that address these important bioinorganic aspects of medicine.

    9: Metals in Medicine (1)

    This chapter introduces three broad aspects of metals in medicine: nutritional requirements and diseases related thereto; the toxic effects of metals; and the use of metals for diagnosis and chemotherapy. Each area is discussed in survey form, with attention drawn to those problems for which substantial chemical information exists. Since there is only a primitive understanding at the molecular level of the underlying biochemical mechanisms for most of the topics, this field is an important frontier area of bioinorganic chemistry. The major focus of this chapter is on the platinum anticancer drug cisplatin, which is presented as a case study exemplifying the scope of the problem, the array of methodologies employed, and the progress that can be made in understanding the molecular basis of a single, if spectacular, metal complex used in medicine today.

    III. Toxic Effects of Metals

    1. Two Classes of Toxic Metal Compounds

    2. Copper Overload and Wilson's Disease8

    3. Iron Toxicity9

    4. Toxic Effects of Other Essential Metals10,11

      (Video) Introduction to Metals in Medicine

    5. Plutonium: A Consequence of the Nuclear Age12

    6. Mercury Toxicity13 and Bacterial Resistance14-17

    7. Cadmium and Lead Toxicity18

    8. Metals as Carcinogens19,20

    9. Summary

    IV. Survey of Metals Used for Diagnosis and Chemotherapy

    1. Radiodiagnostic Agents21,22

    2. Magnetic Resonance Imaging (MRI)27

      (Video) GCSE History: Every Key Individual in Medicine & Public Health (2018)

    3. Lithium and Mental Health28-31

    4. Gold and Rheumatoid Arthritis23,32,33

    5. Anticancer Drugs

      1. Platinum Ammine Halides34,35
      2. Metallocenes and Their Halides: Ti, V, Fe36,37
      3. Gold and Other Metal Phosphines39
      4. Other Main Group and Transition-Metal Compounds36,40,41

    6. Miscellaneous Metals in Medicine

    7. Summary and Prospectus

    V. Platinum Anticancer Drugs: A Case Study

    1. History of Discovery47

    2. Principles that Underlie Drug Development

      1. Strategic Considerations
      2. Pre-clinical and Clinical Trials49
      3. Mechanism of Action Studies
      (Video) Transition Metals in Medicine

    3. Clinical Picture for Cisplatin and Carboplatin49,52

      1. Responsive Tumors and Combination Chemotherapy
      2. Dose-limiting Problems; Toxicology
      3. Pharmacology49,52

    4. Bioinorganic Chemistry of Platinum Anticancer Drugs; How Might They Work?

      1. Reactions of cis-DDP and Related Compounds in Aqueous, Biological, and Other Media
      2. Evidence that DNA is the Target
      3. Aspects of Platinum Binding to DNA
      4. Mapping the Major Adducts of cis- and trans-DDP on DNA; Sequence Specificity
      5. Structure of Platinum-DNA Complexes
      6. Effects of DNA Structure on Platinum Binding
      7. Speculations About the Molecular Mechanism
      8. Site-Specifically Platinated DNA154

    5. Design of New Inorganic Anticancer Drugs

      1. Objectives
      2. Strategies for Drug Development
      3. Second- and Third-generation Platinum Anticancer Drugs
      4. Nonplatinum Antitumor Metal Complexes

    VI. Restrospective

    The topics discussed in this chapter are helping to expand bioinorganic chemistry from a subject that arose chiefly from spectroscopic analysis of metal centers in proteins, because they were uniquely convenient functional groups, to a discipline where fundamental knowledge about metal functions and the application of metals as diagnostic and chemotherapeutic agents are making important contributions to medicine. As the case study of cisplatin is intended to demonstrate, progress in understanding how metals function in chemotherapy can be made only by the combined efforts of many disciplines, including synthetic and physical inorganic and organic chemistry, molecular and cell biology, immunology, pharmacology, toxicology, and clinical medicine. Although we have not yet reached the day where chemotherapeutic agents can be rationally designed from knowledge of a molecular mechanism, such a concept does not seem that farfetched. If nothing else, knowledge of fundamental bioinorganic processes related to metal-macromolecule interactions will continue to grow enormously through efforts to achieve this ultimate goal.

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    162. I am grateful to the Alexander von Humboldt Foundation for a U.S. Senior Scientist Award, Massachusetts Institute of Technology for sabbatical leave time, and Prof. Drs. W. Herrmann and K. Wieghardt for their kind hospitality, all of which were essential for the preparation of the first draft of this chapter during the spring of 1988. I very much appreciate help from the following individuals: A. Davison, for providing Figure 9.2, and D. L. Bancroft, S. F. Bellon, S. L. Bruhn, J. N. Burstyn, K. M. Comess, G. B. Jameson, C. A. Lepre, and J. T. Toney for commenting critically on the manuscript. I also thank M. Mason for typing the first draft.

    Contributors and Attributions

    • Stephen J. Lippard (Massachusetts Institute of Technology, Department of Chemistry)

    Thumbnail: Cisplatin, \(PtCl_2(NH_3)_2\) A platinum atom with four ligands. Image used with permission (Public Domain; Benjah-bmm27).

    (Video) Frontiers in Metals in Medicine Symposium 2020

    FAQs

    What are the heavy metals used in medicine? ›

    Platinum is a precious metal that has been used in a variety of medications and tools since the early 1970s. Its dense, malleable properties are essential to the production of pacemakers, catheters, stents and even cancer therapies.

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    How metals are used in medicine? ›

    Most metals are used as cofactors or prosthetics in enzymes, catalyzing specific reactions and serving essential roles. The essential metals for humans are: Sodium, Potassium, Magnesium, Copper, Vanadium, Chromium, Manganese, Iron, Cobalt, Nickel, Zinc, Molybdenum, and Cadmium.

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    What are the diseases caused by metal deficiency in human body? ›

    Table 9.1 - Essential metals and medical consequences resulting from their deficiency. a
    MetalAbundance Sea Water mg/1 (ppm)Diseases Resulting from Metal Deficiency
    Co1 x 10-4anemia
    Ni2 x 10-4
    Cu3 x 10-3brain disease, anemia, heart disease
    Zn1 x 10-2growth retardation, skin changes
    10 more rows
    May 3, 2023

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    What element is most used in medicine? ›

    Zinc is probably the most frequently used transition metal element in pharmaceutical drugs.

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    What are toxic heavy metals for human health? ›

    The heavy metals most commonly associated with poisoning of humans are lead, mercury, arsenic and cadmium. Heavy metal poisoning may occur as a result of industrial exposure, air or water pollution, foods, medicines, improperly coated food containers, or the ingestion of lead-based paints.

    Learn More Now ›
    What is the most toxic heavy metal? ›

    Mercury. Mercury is considered the most toxic heavy metal in the environment. Mercury poisoning is referred to as acrodynia or pink disease.

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    What metal is used in hospitals? ›

    Copper And Brass

    Brass and copper are mainly used in the medical industry for external hospital equipment. It is used to help transmit signals to diagnostic tools and small implants. Copper also has antimicrobial and antibacterial properties which make it highly suitable in hospital settings.

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    Do we use metals in our daily life? ›

    Some importance of metals in our daily life are: Due to their thermal and electrical conductivity, metals are use to make utensils, cooking vessels, wires and appliances. For example, copper and aluminium are mainly used for these purposes.

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    How can I prevent heavy metals in my body? ›

    Heavy metal detox foods to eat include:
    1. cilantro.
    2. garlic.
    3. wild blueberries.
    4. lemon water.
    5. spirulina.
    6. chlorella.
    7. barley grass juice powder.
    8. Atlantic dulse.

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    Which toxic metal can accumulate in our body and cause chronic diseases? ›

    Mercury is a widespread environmental toxicant and pollutant which induces severe alterations in the body tissues and causes a wide range of adverse health effects [210]. Both humans and animals are exposed to various chemical forms of mercury in the environment.

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    What causes high levels of heavy metals in body? ›

    Heavy metal poisoning is caused by the accumulation of certain metals in the body due to exposure through food, water, industrial chemicals, or other sources. While your body needs small amounts of some heavy metals to function normally — such as zinc, copper, chromium, iron, and manganese — toxic amounts are harmful.

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    What is medicine mostly made of? ›

    These days, medicines come from a variety of sources. Many were developed from substances found in nature, and even today many are extracted from plants. Some medicines are made in labs by mixing together a number of chemicals. Others, like penicillin, are byproducts of organisms such as fungus.

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    What is the most important element in the human body? ›

    Carbon. Carbon is the most crucial structural element and the reason we are known as carbon-based life forms. It is the basic building block required to form proteins, carbohydrates, and fats. Breaking carbon bonds in carbohydrates and proteins is our primary energy source.

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    What is the most common element found in the human body? ›

    Oxygen is the most common element in the human body, comprising approximately 65.0% of body mass. Most of the oxygen present is found in the form of water.

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    How do you detox your brain from heavy metals? ›

    Dietary fiber: Various foods rich in fiber, such as fruit and grains with bran, may help remove heavy metals. Researchers have found fiber to reduce mercury levels in the brain and blood.

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    What are the 5 most toxic heavy metals? ›

    Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic. The industrial activities of the last century have caused massive increases in human exposure to heavy metals. Mercury, lead, chromium, cadmium, and arsenic have been the most common heavy metals that induced human poisonings.

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    What are the three most toxic heavy metals? ›

    Unlike many chemical elements – such as iodine – these 3 metals (mercury, arsenic, and cadmium) offer no benefit to the body. Instead, these heavy metals can be very toxic – disrupting, for instance, many important systems in the body (like the nervous system).

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    What foods contain heavy metals? ›

    Since this contamination has so many different sources, there is a wide range of foods contaminated by heavy metals, including products of plant origin (cereals, rice, wheat, edible roots, mushrooms, etc.) as well as foods of animal origin (fish, crustaceans, mollusks).

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    Where are heavy metals stored in the body? ›

    Once in the body, heavy metals can accumulate over time in your bones, liver, brain, kidneys and heart. Having excess heavy metals in the body can damage vital organs, cause behavioral changes and difficulties with thinking and memory.

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    How long does it take to detox heavy metals from the body? ›

    So, depending on the amount of contamination and the condition of your body, it can take months, sometimes up to a year and a half, to finally get rid of all the toxins and heavy metals. Heavy metals and waste products are excreted by organs such as the liver, spleen, lymph, kidney and intestine.

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    Which metal is vital to human health? ›

    Metals important to our health include calcium, chromium, copper, iron, magnesium, manganese, molybdenum, potassium, sodium and zinc. Our need for many of these metals (like molybdenum, iodine and copper) is so small that you're probably getting them from your diet without even realizing it.

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    What metal is used in surgery? ›

    Stainless steel in medical devices and surgical tools

    Most surgical tools are made from 440 stainless steel. It's not as corrosion resistant as 316 but the higher carbon content means it can be heat treated to create very sharp edges for cutting instruments.

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    What metal is medical grade? ›

    Grade 304 stainless steel is a commonly used, strong, durable, and corrosion resistant medical grade alloy formed from approximately 18% chromium and 8% nickel. The addition of low levels of carbon and manganese allow 304 stainless steel to be resistant to oxidation, making it easy to clean and sterilize.

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    What metals do we use in our daily life? ›

    Nickel, cobalt, and chromium are often found in everyday consumer objects, such as jewelry, clothing, leather, technological devices, household items, and other daily-use objects [1]. Gold, palladium, mercury, copper, aluminum, titanium, iron, platinum, tin, zinc are also occasionally found in these items.

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    What are 10 things made from metal? ›

    Some of the objects made from metal are : Jewellery Wires Utensils Foil paper Statues Gates Nails
    • Jewellery.
    • Wires.
    • Utensils.
    • Foil paper.
    • Statues.
    • Gates.
    • Nails.

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    What are the 10 uses of metals? ›

    • Shiny metals like platinum, gold, and silver are being used for the making of ornaments and pieces of jewelry.
    • Aluminium is being used for the manufacture of insulation wire.
    • Metals like iron and steel are used for building and home constructions to impart strength and durability.

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    What vitamin removes heavy metals? ›

    Fruits and vegetables high in vitamin C can reduce the damage caused by heavy metal toxins by acting as an antioxidant. Vitamin C helps convert toxins into a water-soluble form that may be eliminated easily from the body.

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    Does magnesium get rid of heavy metals? ›

    Magnesium can remove a variety of toxins and heavy metals from your body including aluminum, mercury, and lead. While it's likely that these chemicals will only be present in your body in minute traces, even the tiniest amounts of these can be harmful. As such, flushing them out of your cells is important.

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    What are 4 general symptoms of toxic heavy metal exposure? ›

    Heavy metal poisoning symptoms can vary based on the metal, but some general symptoms that overlap through most instances of excessive exposure to heavy metals include:
    • Nausea and vomiting.
    • Diarrhea.
    • Abdominal pain.
    • Tingling sensation in the hands and feet.
    • Shortness of breath.
    • Sudden chills.
    • Weakness and fatigue.

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    What are the neurological symptoms of heavy metal toxicity? ›

    Conditions resulting from metal exposure may mimic routine neurologic disease, such as encephalopathy (eg, altered mental state), movement disorders (eg, tremor), neuropathy (eg, tingling or numbness in hands and feet), or seizures.

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    What metals causes the most concern? ›

    Arsenic, cadmium, chromium, copper, nickel, lead and mercury are the most common heavy metals which can pollute the environment.

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    How do you check your body for toxic levels? ›

    The only way in which toxins can be checked in the blood is through blood tests. Heavy metal toxicity can result in damage to the vital organs, neurological and muscular degeneration, cancer, allergies and even death.

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    How do you test for metal toxicity in the body? ›

    If you have signs of heavy metal poisoning, your provider may order a heavy metal test. These tests analyze a blood, urine, hair or fingernail sample. Depending on your test results, you may need treatment to reduce the number of heavy metals in your blood.

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    Can your body clear heavy metals? ›

    Our bodies have amazingly complex systems in place to metabolize and eliminate heavy metals, once they enter our bodies. This mostly involves three different mechanisms: Glutathione – A sulfur-containing protein produced within almost all cells of our body, with metal-binding and antioxidant properties.

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    What medication is made from urine? ›

    Menotropin (also called human menopausal gonadotropin or hMG) is a hormonally active medication for the treatment of fertility disturbances. Frequently the plural is used as the medication is a mixture of gonadotropins. Menotropins are extracted from the urine of postmenopausal women.

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    What is the most taken medicine in the world? ›

    The Top 300 Drugs of 2020
    RankDrug NameTotal Prescriptions (2020)
    1Atorvastatin114,509,814
    2Levothyroxine98,970,640
    3Metformin92,591,486
    4Lisinopril88,597,017
    93 more rows
    Sep 12, 2021

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    Is medicine made out of mold? ›

    Medicine. Many common medicines are produced using fungi. Some fungi naturally produce antibiotics to kill or stop the growth of bacteria.

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    What is the most important element in the human survival? ›

    Other than the air we breathe, water is the most essential component for human survival. It is estimated that a person cannot survive for more than 3-4 days without water.

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    What are the top 3 most abundant elements in human body? ›

    By mass, about 96 percent of our bodies are made of four key elements: oxygen (65 percent), carbon (18.5 percent), hydrogen (9.5 percent) and nitrogen (3.3 percent).

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    What are the top 8 elements found in the human body? ›

    About 99% of the mass of the human body is made up of six elements: oxygen, carbon, hydrogen, nitrogen, calcium, and phosphorus. Only about 0.85% is composed of another five elements: potassium, sulfur, sodium, chlorine, and magnesium. All 11 are necessary for life.

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    How many metals are in the human body? ›

    The human body needs about 20 essential elements in order to function properly and among them, for certain, 10 are metal elements, though for every metal we do need, there is another one in our body we could do without it.

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    What are the four elements that help our body grow? ›

    The living body's four primary elements are oxygen, carbon, hydrogen, and nitrogen. It makes up more than 99 percent of the bulk of most cells.

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    What is the most abundant element by mass in the human body? ›

    The most abundant elements by mass in the body of a healthy human adult are: Oxygen (61.4%), Carbon (22.9%), Hydrogen (10.0%) and Nitrogen (2.6%).

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    What are 5 heavy metals that pose health hazards? ›

    Mercury, lead, chromium, cadmium, and arsenic have been the most common heavy metals that induced human poisonings.

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    What are heavy metals in supplements? ›

    Certain dietary supplements or traditional health remedies may be harmful because they contain dangerous chemicals or high levels of heavy metals, such as lead, mercury or arsenic.

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    What everyday products contain heavy metals? ›

    Heavy metals like lead, arsenic, mercury, aluminum, zinc, chromium and iron are found in a wide variety of personal care products including lipstick, whitening toothpaste, eyeliner and nail color. Some metals are intentionally added as ingredients, while others are contaminants.

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    Which heavy metal is used in anticancer medicine? ›

    Platinum compounds, particularly cisplatin, are the heartbeat of the metal-based compounds in cancer therapy.

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    What are 3 heavy metals that are poisonous? ›

    Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure.

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    What heavy metals are in human urine? ›

    The overall mean concentrations of the metals in the urine samples from all the study areas ranged from 0.14 to 0.80 mg/L for lead, 0.55 to 0.93 mg/L for zinc, 1.27 to 3.01 mg/L for iron and up to 0.03 mg/L for copper.

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    What vitamins block heavy metals? ›

    Vitamin B, B-6, and C deficiencies are associated with poor tolerance of heavy metals and easier toxicity. Vitamin C has been reported to have chelating effects on iron. In one animal study, B-1 supplements were shown to decrease iron levels.

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    How can I get rid of heavy metals in my body? ›

    Management and Treatment
    1. Taking chelating agents to remove toxic metals from your body through your urine.
    2. Pumping your stomach (gastric lavage).
    3. Hemodialysis for kidney failure.
    4. Medicines to treat symptoms.
    Jul 7, 2022

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    What are heavy metals to avoid? ›

    Toxic Metals
    • Arsenic. Common sources of exposure to higher-than-average levels of arsenic include near or in hazardous waste sites and areas with high levels naturally occurring in soil, rocks, and water. ...
    • Beryllium. Elemental beryllium has a wide variety of applications. ...
    • Cadmium. ...
    • Hexavalent Chromium. ...
    • Lead. ...
    • Mercury.

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    Does coffee contain heavy metals? ›

    Unfortunately, coffee also contains toxic heavy metals such as cadmium (Cd) and lead (Pb) [16,17,18], although available studies primarily cover instant coffee. The presence of heavy metals in food is a global problem.

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    What vegetables absorb heavy metals? ›

    The concentrations of heavy metals decreased in the sequence as leafy vegetables > stalk vegetables/root vegetables/solanaceous vegetables > legume vegetables/melon vegetables. The ability of leafy vegetables to uptake and accumulate heavy metals was the highest, and that of melon vegetables was the lowest.

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    What are the most cancerous metals? ›

    Arsenic, cadmium, chromium, and nickel are classified as group 1 carcinogens by the International Agency for Research on Cancer, and are utilized commercially. In this review, we used molecular pathway analysis to understand the toxicity and carcinogenic mechanisms of these metals.

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    Which metal is used in chemotherapy? ›

    Platinum is well known for its anticancer activity, firstly used as cis-diaminedichloroplatinum (II) (CDDP), with a wide range of activity. Its main mechanism of action involves its binding to DNA.

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    Which isotope is used to destroy tumors? ›

    Cobalt-60 is most commonly used.

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